Stroke is the largest cause of major disability. This disability most often results from persistent arm impairment. A significant portion of arm impairment is caused not by weakness or spasticity, but by abnormal co-activation among arm muscles. This coordination dysfunction is pervasive in the most severely impaired patients, who are most in need of new therapies. To treat abnormal muscle co-activation, we developed a myoelectric-computer interface (MyoCI). In addition, we pioneered the use of targeted memory reactivation (TMR) to enhance memory consolidation during sleep. The long-term goal of this research is to develop an affordable, non- invasive, and easy-to-use combination of MyoCI and TMR that improves control of arm movements by reducing abnormal co-activation. Our preliminary studies show that TMR enhances consolidation of MyoCI learning in a single nap in a group of healthy individuals, and across several nights in three stroke survivors. Accordingly, we propose to determine whether this training-plus-sleep combination will generalize to improve motor function over an extended training protocol in stroke survivors. The objectives of this proposal are 1) to determine whether TMR can augment motor learning after stroke, and 2) to determine optimal parameters for the MyoCI+TMR paradigm to enhance motor function in stroke survivors. Our central hypothesis is that supplementing MyoCI training with TMR will augment learning considerably and thereby improve arm movement. We will test this hypothesis via the following specific aims: 1) Test the extent to which TMR during SWS enhances MyoCI learning after stroke, 2) Assess the ability of TMR across all sleep stages to enhance MyoCI learning after stroke, and 3) Assess the influence of TMR dose and stroke location on MyoCI learning. This proposal?s innovative combination of wearable, inexpensive, and noninvasive MyoCI+TMR will enable us to test the effects of TMR on motor learning after stroke. Achieving our objectives will be significant because it will facilitate the development of an enhanced rehabilitative therapy to improve function after stroke that could be used widely and could help the most severely impaired stroke survivors. We expect that the paradigm will be synergistic with other therapies, given its novel mechanism of action (reducing co-activation using myoelectric signals). The research will also provide basic information about what brain areas are critical for consolidating motor learning. We further expect that TMR could be applied to other types of stroke rehabilitation in addition to MyoCI. Finally, this project will provide critical information needed to plan larger clinical trials to assess efficacy of this and related approaches.